Background and objective:
Seroepidemiological surveys on SARS-CoV-2 are important to establish trends in population-level immunity. From May 2020 through June 2022, the National Health Institute Doutor Ricardo Jorge implemented four serial studies aimed to estimate post-infection and post-vaccination seroprevalence in Portugal.

Methods:
Overall, surveys covered 19134 Portuguese residents aged 1 or more years old. In each survey, reminiscent blood samples were collected through nationwide network of 43 clinical pathology laboratories and 36 public hospitals to determine SARS-CoV-2 IgG antibody titers. Following vaccination campaign, presence of IgG against nucleocapsid protein (anti-N), was used as a proxy of post-infection seroprevalence in vaccinated.

Results:
Total SARS-CoV-2 seroprevalence varied between 2.9% [95CI: 2.0-4.2] (1st survey, May 21-July 8, 2020) and 95.8% [95CI:95.0-96.4] (4th survey, April 27-June 8, 2022). In the 3rd survey (September 28-November 19, 2021) the post-vaccination seroprevalence was higher than the post-infection 86.3% [95CI:85.1-87.5] vs. 7.5% [95CI:6.6-8.5]. Following the Omicron wave (4th survey), the post-infection seroprevalence increased to 27.3% [95CI:25.5-29.1] for overall population, and to 71.2% [95CI:64.4-77.2] for children aged less than 5 years old, not eligible for COVID-19 vaccination.

_Conclusion_:
Observed trends in seroprevalence were in line with the evolution of the COVID-19 epidemic and vaccination coverage in Portugal, as well as with the results of studies on vaccine effectiveness, demonstrating the importance of seroepidemiological studies for decision making. Implemented infrastructure and acquired experience can be capitalized for the development of seroepidemiological studies in case of future public health emergencies in Portugal.